Free-energy Landscape of Protein by Realistic Lattice Go-like model: Mechanism of Folding and Conformational Change

剣崎 博生

Abstract

Recently, coarse-grained Go-like models based on energy landscape theory
have succeeded in explaining various properties of protein folding.
In this work, we investigate (i) mechanism of protein folding, and
(ii) large conformational changes of motor proteins by using a realistic
lattice Go-like model.
First, how various parameters in the Go-like model influence behaviors
of protein folding is investigated systematically.
Simulation results indicate that (i) the range of attractive interactions
affects largely the cooperativity of folding/unfolding transition,
(ii) folding units are mainly determined by the native topology, and
(iii) the folding order of the folding units is influenced by details
of the native interactions.
Next, we calculate the free-energy landscape of kinesin (motor protein)
and tubulin (rail protein for kinesin).
The free-energy landscape of kinesin shows that kinesin has two
subdomains aside from the hydrophobic core.
These subdomains overlap the regions where important conformational
changes occure during the sliding movement.
Based on simulation results for tubulin, we propose a hypothesis that
a large conformational change of the C-terminal domain of tubulin
plays an active role in the sliding movement.